The objective of this research program is: (1) to define the precursors and pathway(s) involved in the biosynthesis of guanidine in the mammal, (2) to ascertain whether or not guanidine is metabolized in the mammal, and (3) to determine the organ, cell and intracellular distribution of guanidine. This investigation will be carried out using the tissues and various cell preparations from the albino rat. The precursors, and biosynthetic and catabolic pathway(s) will be investigated with the aid of isotopically labeled compounds. Once defined, the enzyme systems involved will be isolated and studied. Sensitive assay systems will be developed for determining the organ, cell and intracellular distribution of guanidine.